Research will be directed at two basic problems in enzyme genetics. The first is concerned with the role of multiple gene loci which determine the structures of organ specific enzymes with very similar but not identical enzymic properties. In particular the biochemical genetics of the alkaline phosphatases will be studied, because previous work indicates that this set of enzymes provides a good model system pertaining to this not uncommon phenomenon. The biochemical, immunological and genetic characteristics of these enzymes in man and also other mammalian species will be examined in order to determine the number of gene loci involved, the differences between their products, their organ specificity and their degree of allelic variation in different species. The aberrant production of alkaline phosphatase by certain cancers and cell lines derived from cancers, will be investigated to determine the nature of this apparent gene derepression and its significance in cancer. The possibility of immunological maternal-fetal incompatibility will be studied by a search for maternal antibodies to placental alkaline phosphatase determined by paternally derived genes in the fetus. This phenomenon could be the cause of certain complications of pregnancy and of fetal abnormality. The second general problem is concerned with the relationship of the physical and functional characteristics of enzymes to genetically determined polymorphism. In particular it is proposed to analyze over an extensive range of enzyme loci the relationships between subunit structure, subunit size and type of reaction catalysed, and the occurrence of enzyme polymorphisms and the frequency of heterozygosities.